This proposal is part of a long {range effort} directed to the discovery of new pharmaceuticals from Peruvian flora traditionally used for the treatment of mental disorders. {Our main hypothesis is that plants ancestrally used by Peruvian traditional healers for treating mental illnesses are a source of novel therapeutics for these disorders. We specifically hypothesize that: 1) it is possible to isolate bioactive principles from these plants;2) rodent behavioral models are a good start point tool for screening/validation and for further prioritization of research on those activities; 3) the isolated lead compounds will be superior to those obtained from chemical libraries in terms of better bioavailability and less secondary effects; 4) the pharmacological information obtained will help to further understand the traditional medicine conceptualization of mental disorders in Peru. Previous studies have led us} to collect information on the traditional use of plants for the treatment of mental disorders in several Peruvian localities and geographical regions. We currently have extracts from 475 plant collections corresponding to 265 species from 87 different plant families. These plants are traditionally used for one or more of the following activities: antipsychotic, antidepressant, anxiolytic and sedative. {Importantly}, about 65% of those species have never been described in the scientific literature for their potential effects on the modulation of behavior. About {20%} of these plant extracts have been screened so far to validate its traditional medical use with behavioral tests in mice. To date we have identified {70} extracts having one or more potential psychotropic activity ({54} antipsychotic, {40} anxiolytic and {17} antidepressant). {Dose-response curves have been run for 9 of these extracts.} In this R21 we are proposing to {run 30 additional dose-response curves and pursue the activity guided fractionation of at least 1 extract. We have especial interest in developing or testing} new methods for the screening and bioassay guided fractionation of our extracts, in order to identify novel agents that could be candidate drugs or lead compounds for mental disorders. Also, we aim to get further insight on the Peruvian traditional medicine conceptualization of mental disorders, by comparing the pharmacological/behavioral results obtained in our experiments with the reported/interpreted traditional use. A multidisciplinary group of {professionals, leaders in their area of expertise,} has been invited to participate in this R21, which will end up in the preparation of an R01 proposal. Screening natural product extracts for mental disorders has led to the discovery of therapeutic agents in use today, and, although discovery of a new agent is obviously an ambitious goal, there are numerous factors that support the likelihood of being able to successfully identify novel agents that are candidate drugs or lead compounds for mental disorder treatment. These factors include the innovative screening approach, the uniqueness of our natural product library, the multidisciplinary nature of the project, and the expertise of the team of investigators and consultants.